The committee considered a review it had commissioned of the existing literature on experimental studies that might meet criteria for the second event hypothesis. The aim of the review was to find out whether there is biological evidence that sheds light on the importance or otherwise of second events (see summary of meeting 5). The committee then went on to discuss various biological aspects of the second event theory.


The review commissioned for the committee showed that there are only a few results in the literature on very low level exposure to radionuclides such as strontium-90 that are relevant to second event theory. The author of the review found that there are only one, or possibly two, cases of data that cannot be explained in terms of current models. He concluded that it is not possible to exclude totally an increased effect at low doses and dose rates, but that the bulk of the evidence indicates that there is no such effect. He was also of the opinion that it is debatable whether any effect arises from second events or from some other mechanism.

Some members of the committee had difficulties with the content of the review and disagreed with its conclusions. They felt that a number of studies cited in the review, and some omitted from it, do provide evidence that second events are important or potentially important. The review was useful in identifying the types of past experimental studies that could be relevant to testing the second event theory but they did not accept its overall findings. In the view of these members, the problem is that it is necessary to look for subtle effects at low doses and the appropriate experimental work has not yet been done.


The committee discussed three key biological assumptions that seem to be inherent in the second event theory as it was originally stated. These assumptions are:

1. low doses of radiation (even a single electron) cause resting cells to move into ‘repair/replication’ cycle;
2. repair of low dose damage triggers a resting cell into replication and commits it to go through a cycle;
3. dividing cells are hundreds of times more sensitive to radiation damage and mutation than resting cells.

In discussion of assumptions (a) and (b), various members of the committee said that cells mostly repair themselves while resting, without moving into cycle, and that insults to cells generally stopped them from cycling rather than triggering them into cycle. These members stated that damaged cells do not normally replicate. Other members said that text books on radiation biology state that cells would replicate when insulted by radiation. There was also a suggestion by members that there might be confusion in some of the literature between repair and replication, which are very different things. With reference to assumption (c), some members said that most of the existing data indicate that replicating cells are typically two to five times more sensitive to radiation than resting cells. Other members were of the view that key cells for some cancers are hundreds of times more sensitive when replicating.


Bimodal (also called biphasic) dose responses are those in which the effect of the radiation on the cell or organism increases with dose until it reaches a maximum at a relatively low dose, then decreases with increasing dose, then increases with increasing dose again. There are a considerable number of experimental studies that show bimodal (or more complex) dose responses at the cellular level. Also, some epidemiological studies of workers and of the public can be interpreted as showing bimodal responses to radiation. Various non-radioactive substances seem to have bimodal intake/effect relationships in animals and people.

Two biological explanations are commonly put forward to account for bimodal dose responses to radiation. One is that there is a sub-class of cells that is more sensitive to radiation than most cells. Effects on this sub-class lead to the low dose maximum and effects on the other cells lead to the subsequent increase with increasing dose. The other explanation is that repair of radiation damage to cells only occurs when doses reach a particular level. The absence of repair at very low doses means effects are greater than at higher doses.

Some members of the committee feel that the evidence for bimodal dose response relationships for radiation health effects in people is not convincing. They interpret the data at low doses as scatter around a straight line. Some of these members are also of the view that many of the effects seen at the cellular level are transitory and are unlikely to lead to long term consequences for an organism. Other members feel that the evidence is fairly convincing. In their view there are enough studies with results that show a bimodal relationship to make it likely that the dose response relationships for many of the detrimental effects of radiation on human health are bimodal.

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